Viral adaptation to host: a proteome-based analysis of codon usage and amino acid preferences

Bahir, Iris; Fromer, Menachem; Prat, Yosef; Linial, Michal

We set out to test the preference of amino acids in viral proteomes vis-a-vis their hosts. To this end, we compiled an exhaustive representative set (see Materials and methods) and applied the virus-to-host mapping at a high taxonomical level ( Figure 2 , level C). To start with, we focused on two taxonomical groups: mammals (subdivided into human and nonhuman hosts) and bacteria. This analysis is based on 481 779 and 312 201 amino acids from the respective virus groups. The proteomes of virus representatives that infect humans and those that infect bacteria (bacteriophages) are compared ( Figure 3A ). It is evident that some amino acids Figure 2 Mapping of viruses to hosts. (Top) a tree is drawn according to the hierarchical taxonomy of the hosts (from class to genus, based on NCBI taxonomy). The hosts that are unified at the suborder level are framed with an identical color. The four levels (A-D) represent the host grouping at the genus, suborder, order, and class levels, respectively. Below each host, the viruses that infect it are listed. (Bottom) for each taxonomy level, the virus-to-host mapping resulting from the tree is shown. Ambiguity in mapping of viruses to their hosts results from viruses that are annotated to infect a group of hosts that are not uniquely defined at the taxonomical level of interest (e.g., V5 not uniquely defined at level B strongly deviate between these two groups. For example, arginine (R) is more prevalent in the viruses of humans (Po10 À6 , t-test with Bonferroni correction), whereas lysine (K) appears more in bacterial proteomes (Po10 À6 ). A similar trend is seen for isoleucine (I, Po10 À6 ) and leucine (L, Po10 À6 ). The source and biological significance of such differences are under study and beyond the scope of this study. Similarly, we measured the codon usage for each of the 59 codons that code for 1 of the 18 degenerately encoded amino acids (tryptophan and methionine are encoded by only a single codon). As an illustration, we show the codon preferences for arginine (R, 6 codons) and leucine (L, 6 codons), as measured for human-infecting and mammalian (excluding human) virus groups ( Figure 3B ). The different usage of each of the amino acids' codon triplets is evident (w 2 test, Po10 À6 ).